• SCID-X1 Gene Therapy Trial

    Gene Therapy

    Phone: 617-632-5064  

    Gene Transfer for SCID-X1 Using a Self Inactivating (SIN) Gammaretroviral Vector

    A Multi-Institutional Phase I/II Trial Evaluating the Treatment of SCID-X1 Patients with Retrovirus-mediated Gene Transfer

    X-linked severe combined immunodeficiency (SCID-X) is a rare genetic immunodeficiency that prevents a child's bone marrow from producing infection-fighting white blood cells.

    Recent clinical trials for SCID-X1 documented the efficacy of gene transfer in SCID, although there was some toxicity related to insertional mutagenesis. This Phase I/II gene therapy trial for patients with SCID-X1 utilizes a new, safer virus vector developed collaboratively with investigators around the world.

    • We have designed a novel self inactivating (SIN) vector, pSRS11.EFS. IL2RG. pre*, which lacks all enhancerpromoter elements of the LTR U3 region and is devoid of all gammaretroviral coding regions.
    • Expression of the therapeutic gene is regulated by an internal housekeeping gene promoter derived from human elongation factor-1 (EF-1) gene.
    • This vector, which expresses the IL2RG gene, has reduced mutagenic potential compared to LTR configuration in non-clinical studies.
    • Based on experience in other transplant and gene therapy trials, we recently modified the protocol to include low dose Busulfan conditioning in patients without active infections, in order to enhance correction of humoral (B cell) immunity.

    SCID-X1 Trial Inclusion Criteria

    Patients must have a definitive diagnosis of SCID-X1 with no HLA-matched family donors available, and be either

    • 3.5 months old and lack an HLA identical (A,B,C,DR,DQ) unrelated donor OR
    • of any age with an active, therapy-resistant infection or other medical conditions that significantly increase the risk of allogeneic transplant¬†

    As of November 2016, this Phase I/II trial has enrolled seven patients in the United States and six patients in Europe. Preliminary outcome data from this trial were published in Hacein-Bey-Abina S, et al. N Engl J Med 2014 Oct 9;371(15):1407-17.